Freeze-drying method of recombinant human pro-urokinase for injection

A technology for prourokinase and injection, which is applied in the field of lyophilization of recombinant human urokinase for injection, which can solve the problems of inconvenience, easy collapse of lyophilized powder, and low eutectic point

Pending Publication Date: 2021-07-16
TASLY BIOPHARMACEUTICALS CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] But the existing method still has the following disadvantages: 1, the prescription of the 5 mg preparation specification of recombinant human urokinase for injection (Pro-UK) that has been listed on the market is applied to clinical practice, and one-time medication needs to use 10, which is extremely inconvenient
2. During the freeze-drying process of the preparation, the eutectic point is low, and the freeze-dried powder of 5mg preparation is slightly loose, and the freeze-dried powder is still easy to collapse

Method used

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  • Freeze-drying method of recombinant human pro-urokinase for injection
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  • Freeze-drying method of recombinant human pro-urokinase for injection

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0120] Embodiment 1: Raw material of prourokinase freeze-dried powder for injection

[0121] It is made of the following components by weight (1000 tubes as an example): 10.7g of prourokinase, 500ml of phosphate buffer, 120g of mannitol, 6g of human serum albumin, supplemented with water to 2000ml, and pH adjusted to 6.9±0.5 .

Embodiment 2

[0122] Embodiment 2: freeze-drying process

[0123] 1. Product pre-freezing and annealing: After filling, put the product into a freeze-drying box for product pre-freezing. During the pre-freezing process, the set temperature of the plate layer is -40°C. See the table below for each parameter setting. After the product temperature is stable Anneal at -25°C;

[0124] Table 10: Setting of prefreezing parameters

[0125] Set temperature(°C) Setting time (min) Duration (min) Phase 1 -2 1 30 Phase 2 -40 60 60 Phase 3 -25 10 120 Phase 4 -40 30 90

[0126] 2. Primary drying: During the primary drying process, the freeze-drying box needs to be aerated, and the air aeration is controlled between 20±5Pa, and the temperature of the plate layer rises to -20℃~-10℃. The parameters are set in the table below, and Hold steady until the product waterline disappears.

[0127] Table 11: Parameter settings for primary drying

[0128] ...

experiment example 1

[0132] Experimental Example 1: Analyzing the Drying and Screening Process

[0133] On the basis of pre-freezing parameters, annealing parameters and primary drying parameters, the secondary drying is carried out, that is, the optimization of analytical drying parameters. During the research process, three groups of experiments TA, TB and TC were designed. The analysis temperature of group TA was set at 30°C, that of group TB was set at 35°C, and that of group TC was set at 40°C. The specific parameters of each stage are controlled as shown in Table 13:

[0134] Table 13: Analytical drying optimization experimental parameters

[0135]

[0136] The parameters in Table 13 show that after pre-freezing at -40°C, annealing at -25°C is carried out, drying is carried out at -10°C once, and then the temperature rises to 30°C, 35°C, and 40°C for analytical drying until the pressure rise does not exceed 0.01 After mbar / min, the plug is fully pressed out of the box. According to the...

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Abstract

The invention relates to a freeze-drying method of recombinant human pro-urokinase for injection, which comprises the following steps: 1) pre-freezing and annealing of a product, mixing raw materials and auxiliary materials and subpackaging into penicillin bottles, then putting into a freeze-drying box for pre-freezing the product, setting the temperature of a plate layer to be-38 DEG C to-42 DEG C in the pre-freezing process, keeping for 50-70 minutes, and annealing at-22 to-28 DEG C after the temperature of the product is stable; 2) primary drying: a freeze-drying box body needs to be aerified, the aerification is controlled to be 20 + / -5 Pa, and the temperature of a plate layer is raised to-20 DEG C to-10 DEG C and is kept stable until the waterline of a product disappears; and 3) secondary drying (desorption drying): after the primary drying is finished, the temperature of the plate layer is raised to 30-40 DEG C, secondary drying is carried out, and the drying temperature is controlled to be 35 + / -5 DEG C.

Description

technical field [0001] The invention relates to a preparation method of a pharmaceutical preparation, in particular to a freeze-drying method of recombinant human urease for injection. Background technique [0002] Prourokinase (Prourokinase, referred to as pro-UK) is a kind of serine protease, which can activate plasminogen in the body to convert into active plasmin, thereby dissolving fibrin in thrombus, so it has great significance in the treatment of thrombus. Wide range of applications. [0003] The peptide bond between Lys158-Ile159 in pro-UK is easily hydrolyzed by plasmin and other enzymes to generate urokinase (UK for short). UK consists of two peptide chains, A chain and B chain, connected by interchain disulfide bonds. Compared with UK, pro-UK has a higher affinity with fibrin, and the site of activating the fibrinolytic system is often at the site of thrombus formation, so the side effects of systemic bleeding tendency are smaller than that of urokinase, and it...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/19A61K38/49A61K47/26A61K47/42A61K47/02A61P7/02
CPCA61K9/19A61K9/0019A61K38/49C12Y304/21073A61K47/26A61K47/42A61K47/02A61P7/02
Inventor 闫凯境莫英韩进赵先锋
Owner TASLY BIOPHARMACEUTICALS CO LTD
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